嗅觉障碍与阿尔茨海默病中的 Tau 病理学和神经炎症有关。
Olfactory Impairment Is Related to Tau Pathology and Neuroinflammation in Alzheimer's Disease.
机构信息
Taub Institute, Columbia University Irving Medical Center, New York, NY, USA.
Weill Cornell Medical College, New York, NY, USA.
出版信息
J Alzheimers Dis. 2021;80(3):1051-1065. doi: 10.3233/JAD-201149.
BACKGROUND
Olfactory impairment is evident in Alzheimer's disease (AD); however, its precise relationships with clinical biomarker measures of tau pathology and neuroinflammation are not well understood.
OBJECTIVE
To determine if odor identification performance measured with the University of Pennsylvania Smell Identification Test (UPSIT) is related to in vivo measures of tau pathology and neuroinflammation.
METHODS
Cognitively normal and cognitively impaired participants were selected from an established research cohort of adults aged 50 and older who underwent neuropsychological testing, brain MRI, and amyloid PET. Fifty-four participants were administered the UPSIT. Forty-one underwent 18F-MK-6240 PET (measuring tau pathology) and fifty-three underwent 11C-PBR28 PET (measuring TSPO, present in activated microglia). Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ42).
RESULTS
Low UPSIT performance was associated with greater18F-MK-6240 binding in medial temporal cortex, hippocampus, middle/inferior temporal gyri, inferior parietal cortex, and posterior cingulate cortex (p < 0.05). Similar relationships were seen for 11C-PBR28. These relationships were primarily driven by amyloid-positive participants. Lower UPSIT performance was associated with greater CSF concentrations of t-tau and p-tau (p < 0.05). Amyloid status and cognitive status exhibited independent effects on UPSIT performance (p < 0.01).
CONCLUSION
Olfactory identification deficits are related to extent of tau pathology and neuroinflammation, particularly in those with amyloid pathophysiology. The independent association of amyloid-positivity and cognitive impairment with odor identification suggests that low UPSIT performance may be a marker for AD pathophysiology in cognitive normal individuals, although impaired odor identification is associated with both AD and non-AD related neurodegeneration.NCT Registration Numbers: NCT03373604; NCT02831283.
背景
嗅觉障碍在阿尔茨海默病（AD）中很明显；然而，其与 Tau 病理学和神经炎症的临床生物标志物测量的确切关系尚不清楚。
目的
确定使用宾夕法尼亚大学嗅觉识别测试（UPSIT）测量的嗅觉识别性能是否与 Tau 病理学和神经炎症的体内测量有关。
方法
从一个由 50 岁及以上成年人组成的既定研究队列中选择认知正常和认知受损的参与者，这些参与者接受了神经心理学测试、脑 MRI 和淀粉样蛋白 PET。54 名参与者接受了 UPSIT 测试。41 人接受了 18F-MK-6240 PET（测量 Tau 病理学），53 人接受了 11C-PBR28 PET（测量 TSPO，存在于激活的小胶质细胞中）。23 名参与者进行了腰椎穿刺，以测量 CSF 中总 Tau（t-tau）、磷酸化 Tau（p-tau）和淀粉样蛋白-β（Aβ42）的浓度。
结果
UPSIT 表现较差与内侧颞叶皮层、海马体、中/下颞叶回、下顶叶皮层和后扣带回皮层 18F-MK-6240 结合增加相关（p < 0.05）。11C-PBR28 也存在类似的关系。这些关系主要是由淀粉样蛋白阳性参与者驱动的。UPSIT 表现较差与 CSF 中 t-tau 和 p-tau 浓度增加相关（p < 0.05）。淀粉样蛋白状态和认知状态对 UPSIT 表现有独立影响（p < 0.01）。
结论
嗅觉识别缺陷与 Tau 病理学和神经炎症的程度有关，特别是在有淀粉样蛋白病理生理学的患者中。淀粉样蛋白阳性和认知障碍与气味识别的独立相关性表明，UPSIT 表现不佳可能是认知正常个体 AD 病理生理学的标志物，尽管嗅觉识别障碍与 AD 和非 AD 相关的神经退行性变有关。
NCT 注册号：NCT03373604；NCT02831283。
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